Ankylosing spondylitis (AS) is an inflammatory joint disease affecting the axial skeleton, peripheral joints, entheses, and extra-articular site. Non-steroidal anti-inflammatory agents are the first line drugs for treatment of AS. Sulfasalazine is regarded as the second line drug and is usually used on AS patients with concomitant peripheral arthritis. Sulfasalazine has side effects, including liver toxicity, hematological abnormality, skin eruption, and other symptoms. However, eosinophilic pleural effusion is rare. Thus, we report on a patient with peripheral eosinophilia and eosinophilic pleural effusion after taking sulfasalazine for treatment of AS.